Diagnostic performance of β-(1→3)-D-glucan, two Candida antigen, and five anti-Candida antibody assays in ICU patients with sepsis and high risk for invasive candidiasis: a secondary endpoint of the CandiSep randomized clinical trial

Standl L, Huber T, Bloos F, Thomas-Rüddel D, Träger J, Kluge S, Fichtner F, Simon P, Kogelmann K, de Heer G, Kuhn SO, Jarczak D, Motsch J, Hempel G, Weiler N, Weyland A, Drüner M, Gründling M, Meybohm P, Richter D, Moerer O, Günther U, Schädler D, Zarbock A, Putensen C, Castellanos I, Kurzai O, Schlattmann P, Cornely OA, Bauer M, Lehmann T, Valenza G, Bogdan C, Held J (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 64

Article Number: e0150025

Journal Issue: 5

DOI: 10.1128/jcm.01500-25

Abstract

Invasive Candida infection (ICI) is the most common fungal infection in critically ill patients. This study analyzed the performance of various biomarkers in sera from the CandiSep trial, a randomized, multicenter trial including 342 sepsis patients at high risk for ICI across 18 German intensive care units. ICI and candidemia were diagnosed in 48 (14.0%) and 14 (4.1%) patients, respectively. Sera collected on 2 consecutive days at sepsis onset were analyzed for β-(1→3)-D-glucan (BDG; Fungitell), mannan (Platelia-Candida-Ag-Plus [Platelia-Mn] and Serion-ELISA-antigen-Candida [Serion-Mn]), and anti-Candida antibodies (Platelia-Candida-Ab-Plus, Serion-ELISA-Candida albicans-IgA/IgM/IgG, and Virclia-Candida albicans-germ-tube-antibody-IgG-Monotest). Only antigen levels (BDG, Platelia-Mn, Serion-Mn), but not anti-Candida antibody levels, were significantly elevated in ICI patients. Antigen levels were unaffected by Candida colonization, while antibody levels were significantly increased. Sensitivity and specificity at the manufacturer’s cutoffs were unsatisfactory. Performance improved by adjusting cutoffs: BDG required a 3-fold increase, while all others required lowering. At 80% specificity, sensitivities (95% confidence intervals) for the diagnosis of ICI and candidemia were as follows: BDG (cutoff >280 pg/mL), 46% (31.4–60.8) and 64% (35.1–87.2); Platelia-Mn (cutoff >50 pg/mL), 38% (24.0–52.6) and 64% (35.1–87.2); Serion-Mn (cutoff >0.7 U/mL), 38% (24.0–52.6) and 50% (23.0–77.0), and below 28% and 43% for all antibody assays. Area under the receiver operating characteristic curve comparisons showed no significant differences between antigen assays. Combining biomarkers, either simultaneously or sequentially, offered no diagnostic advantage over single-biomarker use. In conclusion, anti-Candida antibody assays are likely influenced by colonization and have limited diagnostic utility. Antigen assays offer similar diagnostic value but require cutoff optimization. Combining biomarkers did not enhance diagnostic yield in our cohort.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Bonn Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universität Leipzig Germany (DE) Universität Augsburg Germany (DE) Klinikum Leer gGmbH Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Köln Germany (DE) Hochschule Emden/Leer Germany (DE) Carl von Ossietzky Universität Oldenburg Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Göttingen Germany (DE)

How to cite

APA:

Standl, L., Huber, T., Bloos, F., Thomas-Rüddel, D., Träger, J., Kluge, S.,... Held, J. (2026). Diagnostic performance of β-(1→3)-D-glucan, two Candida antigen, and five anti-Candida antibody assays in ICU patients with sepsis and high risk for invasive candidiasis: a secondary endpoint of the CandiSep randomized clinical trial. Journal of Clinical Microbiology, 64(5). https://doi.org/10.1128/jcm.01500-25

MLA:

Standl, Lea, et al. "Diagnostic performance of β-(1→3)-D-glucan, two Candida antigen, and five anti-Candida antibody assays in ICU patients with sepsis and high risk for invasive candidiasis: a secondary endpoint of the CandiSep randomized clinical trial." Journal of Clinical Microbiology 64.5 (2026).

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